Opioid dependence is an enduring public health problem and the severity of that problem has escalated dramatically because of its association with IV drug use and AIDS. Although opioid dependence is frequently acknowledged as a problem of urban areas, what has been less frequently acknowledged is that opiold dependence occurs in, and is a public health problem for, rural areas. Such a lack of recognition has often led to a paucity of treatment alternatives for the opiold dependent individual in these rural areas. In this application, we propose to establish the first outpatient detoxification clinic to provide pharmacotherapies for opioid dependence in the State of Vermont. Approximately 20 patients per year will participate in clinical pharmacology studies to examine a promising new opiold treatment agent - buprenorphine. Although buprenorphine has several advantages over existing pharmacotherapies, considerably more needs to be known about its clinical pharmacology so that it can be used with the greatest efficacy and efficiency. The focus of our investigations will be to answer questions about buprenorphine's clinical pharmacology that will directly impact the manner in which buprenorphine will be used in treatment settings. Specifically, in a series of 10 clinical pharmacology studies, we will answer the following three questions: (1) what are the range of conditions under which methadone-maintained patients can be transferred to buprenorphine without precipitating withdrawal? (2) What is the duration of buprenorphine's blockade of the effects of morphine-like opioids? (3) What is the feasibility of a buprenorphine/naltrexone combination product? These studies will occur in the first few months of a six month detoxification program. Moreover, given that opiold-dependent individuals must be detoxified from buprenorphine treatment, we will maximize the resources of this proposed project by randomly assigning subjects to different double-blind buprenorphine detoxification schedules. This study will provide information about the most efficacious way to detoxify individuals on from buprenorphine. If NIDA were to Identify some other promising new agent, we would integrate and examine the clinical pharmacology of that new compound as well. The adjunct psycho-social therapy will be one that we have developed from an existing NIDA grant and that our data suggests will have positive clinical impact. This project will provide information about the clinical pharmacology of buprenorphine which should enhance the treatment of opioid dependence and will establish the first outpatient pharmacotherapy for opiold dependence in the State of Vermont.